Braithwaite et al. International Journal of Pediatric Endocrinology 2012, 2012:27 http://www.ijpeonline.com/content/2012/1/27
RESEARCH
Open Access
FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study Vickie Braithwaite1*, Andrew M Prentice2,3, Conor Doherty2,3 and Ann Prentice1,3
Abstract Background: Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation. Study design and methodology: Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate. The children were from a rural Gambian population where rates of iron deficiency and infection/inflammation are high. This study identified cross-sectional and longitudinal relationships between FGF23, inflammation (C-reactive protein (CRP)) and iron status (ferritin, haemoglobin, and zinc protoporphyrin). CRP ≥ 5 mg/dL was used to indicate inflammation and FGF23 ≥ 125 RU/mL was considered elevated. Results: FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=−0.57 (0.12), R2=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=−0.89 (0.14), R2=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =−0.41 (0.11), R2=14.1%, P=0.0004; haemoglobin=−2.22 (0.64), R2=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R2=18.6%, P≤0.0001) and multivariate analysis (R2=33.1%; ferritin=−0.36 (0.10), P=0.0007, haemoglobin = −1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02). Conclusions: Iron status rather than inflammation is a negative predictor of plasma FGF23 concentration. Improvements in iron status following iron supplementation are associated with a significant decrease in FGF23 concentration. Keywords: Fibroblast growth factor-23, Iron status, Inflammation, Africa, Iron supplementation
Background Fibroblast growth factor-23 (FGF23) is a bone derived, phosphate regulating hormone which is often elevated in genetic hypophosphataemic disorders [1] and in chronic kidney disease [2]. Recent studies have identified relationships between FGF23 and various markers of iron status. These include an inverse correlation * Correspondence:
[email protected] 1 MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge CB1 9NL, United Kingdom Full list of author information is available at the end of the article
between FGF23 and serum iron (Fe) [3,4], haemoglobin (Hb) [5], and ferritin (Ferr) [6]. However each of these markers of iron status is affected by the acute phase response and consequently they have limited use as markers of nutritional iron status when used in isolation from markers of inflammation [7]. It is plausible that the inverse correlation between markers of iron status and FGF23 [3-6] is the result of confounding by the inflammatory response. The potential role of the inflammatory response in FGF23 pathways has not yet been considered [8].
© 2012 Braithwaite et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Braithwaite et al. International Journal of Pediatric Endocrinology 2012, 2012:27 http://www.ijpeonline.com/content/2012/1/27
The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron and FGF23 whilst correcting for inflammation and c) to assess the change of FGF23 after supplementation with iron. The study used data from children in a rural Gambian population where dietary calcium intakes are low, rates of iron deficiency [9] and infection are high, and where a wide range of FGF23 concentrations have been reported [5].
Methods Subjects and study information
A subset of samples (n=79) from a cohort of children (n=821) who participated in a non-controlled iron supplementation study designed to assess the variability of response to supplementation during the malaria season were included in this study. The children in the cohort were recruited from the local community in West Kiang, The Gambia and were aged between 0.5-7.0 y. Baseline measurements and start of supplementation were conducted in August 2004 and post supplementation measurements were conducted in December 2004 [10]. Subjects were given Fe 6x/week for three months in the form of Fe sulphate tablets (Nutriset, Malaunay, France). Daily consumption of the supplement was supervised by trained fieldworkers. The dose given was dependent on age and, if present, the severity of baseline anaemia (
